7. Understanding the selectivity of antitumor drugs that target metastasis

Organometallic RAPTA compounds, [(h6-arene)RuCl2(pta)] (where pta = 1,3,5-triaza-7-phospha-adamantane) and NAMI-A (new anti-tumour metastasis inhibitor), have been shown to be only poorly toxic towards cancer cells and completely non-toxic towards healthy cells in vitro [1]. One of these compounds (RAPTA-C) was found to inhibit lung metastases in vivo in CBA tumour mice in the absence of effects on the primary tumour. The reason for the selective inhibition of metastasis by RAPTA-C is not yet known. To better understand the in vivo distribution and activity of RAPTA-C, it is of crucial importance to assess the biodistribution of these new compounds via non-invasive imaging technologies in order to understand their lower toxicity in normal cells and their selectivity in vitro and in vivo.

The project intended to prepare, characterize and employ radiolabeled analogues of the parent RAPTA-C and NAMI-A drugs for in vivo and in vitro biodistribution assays. For this purpose it was the aim to assess both radiosynthetic strategies: (i) either a prosthetic group labelled with 18F should be conjugated to the metal complex or (ii) radioactive ruthenium (e.g. 103Ru) should be employed to prepare complexes of this radiometal